β-sitosterol,an important component in the fruits of Alpinia oxyphylla Miq.,prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway
10.12122/j.issn.1673-4254.2025.08.19
- VernacularTitle:益智仁提取物谷甾醇通过抑制铁死亡中的ETS-5基因表达延长秀丽隐杆线虫的寿命
- Author:
Junyi LI
1
;
Siyuan CHEN
;
Liyao XIE
;
Jin WANG
;
Ao CHENG
;
Shaowei ZHANG
;
Jiyu LIN
;
Zhihan FANG
;
Yirui PAN
;
Chonghe CUI
;
Gengxin CHEN
;
Chao ZHANG
;
Li LI
Author Information
1. 南方医科大学 第一临床医学院,广东 广州 510000
- Publication Type:Journal Article
- Keywords:
β-sitosterol;
senescence;
ferroptosis;
ETS-5
- From:
Journal of Southern Medical University
2025;45(8):1751-1757
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the anti-aging effect of β-sitosterol(BS),an important component in the fruits of Alpinia oxyphylla Miq.,in C.elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.Methods C.elegans treated with 10 μg/mL BS were monitored for survival time and changes in body length,motility,and reproductive function.The effect of ETS-5 gene knockdown on survival time of C.elegans was observed,and the changes in fat accumulation and lipid redox homeostasis in the transfected C.elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio.The mRNA expression levels of ferroptosis-related genes(FTN-1,GPX-1 and AAT-9)were detected using qPCR.The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C.elegans were examined.The effect of BS on nuclear localization of FEV(the human homolog of ETS-5)was validated in cultured human umbilical venous endothelial cells(HUVECs).Results Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan,promoted lipid accumulation and reduced lipid peroxidation in C.elegans.ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1,AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C.elegans.Conclusion BS inhibits ferroptosis in C.elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme,a key gene for ferroptosis,which in turn prolongs the lifespan of C.elegans.
